Cognitive ability may decline as a normal consequence of aging or as a consequence of a CNS disorder.
For example, a significant population of elderly adults experiences a decline in cognitive ability that exceeds what is typical in normal aging. Such age-related loss of cognitive function is characterized clinically by progressive loss of memory, cognition, reasoning, and judgment. Mild Cognitive Impairment (MCI), Age-Associated Memory Impairment (AAMI), Age-Related Cognitive Decline (ARCD) or similar clinical groupings are among those related to such age-related loss of cognitive function. According to some estimates, there are more than 16 million people with AAMI in the U.S. alone (Barker et al., 1995), and MCI is estimated to affect 5.5-7 million in the U.S. over the age of 65 (Plassman et al., 2008).
Cognitive impairment is also associated with other central nervous system (CNS) disorders, such as dementia, Alzheimer's Disease (AD), prodromal AD, post traumatic stress disorder (PTSD), schizophrenia, bipolar disorder (e.g., mania), amyotrophic lateral sclerosis (ALS), cancer-therapy-related cognitive impairment, mental retardation, Parkinson's disease (PD), autism, compulsive behavior, and substance addiction.
There is, therefore, a need for effective treatment of cognitive impairment associated with central nervous system (CNS) disorders and to improve cognitive function in patients diagnosed with, for example, age-related cognitive impairment, MCI, amnestic MCI, AAMI, ARCD, dementia, Alzheimer's Disease (AD), prodromal AD, post traumatic stress disorder (PTSD), schizophrenia, bipolar disorder (e.g., mania), amyotrophic lateral sclerosis, cancer-therapy-related cognitive impairment, mental retardation, Parkinson's disease (PD), autism, compulsive behavior, and substance addiction, and similar central nervous system (CNS) disorders associated with cognitive impairment or at risk of developing them.
Levetiracetam is a widely used antiepileptic drug. Its International Union of Pure and Applied Chemistry (IUPAC) name is (2S)-2-(2-oxopyrrolidin-1-yl) butanamide) and its chemical structure is shown in Formula I.

Levetiracetam is indicated as adjunctive therapy in the treatment of partial onset seizures, or myoclonic seizures, or primary generalized tonic-clonic seizures. It is recommended that such treatments should be initiated with a daily dose of 1000 mg/day. Additional dosing increments may be given to a maximum recommended daily dose of 3000 mg. Levetiracetam is currently available as immediate and extended release formulations for oral administration. Extended release dosage form of levetiracetam is available in strengths of 500 mg, 750 mg, and 1000 mg for once daily usage. Immediate release dosage form of levetiracetam is available in strengths of 250 mg, 500 mg, 750 mg, and 1000 mg for twice daily usage.
International Application Nos. PCT/US09/05647, PCT/US12/24556, and PCT/US14/29170 disclose that levetiracetam, when administered at a dose lower than the therapeutic doses for treating epilepsy, can treat cognitive impairment associated with central nervous system (CNS) disorders in a subject in need or at risk thereof.
The currently commercially available extended release dosage forms of levetiracetam comprise 500 mg, 750 mg, and 1000 mg of levetiracetam. Such extended release dosage forms are not suitable for treating cognitive impairment. There is, therefore, a need for novel extended release compositions of levetiracetam for treating cognitive impairment.